Rytary: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on April 3, 2023.

1. How it works

• Rytary is a brand (trade) name for a combination extended-release capsule containing carbidopa and levodopa which may be used to treat Parkinson's disease or parkinsonism caused by other factors.
• Research has shown that Parkinson's disease is related to the depletion of dopamine in the brain. Administering dopamine to treat Parkinson's disease is ineffective because it does not cross the blood-brain barrier. But levodopa, a precursor of dopamine, does cross the blood-brain barrier and appears to be converted to dopamine in the brain. However, large amounts of levodopa are decarboxylated before it even reaches the brain so carbidopa is added which inhibits the decarboxylation of peripheral levodopa. Carbidopa does not cross the blood-brain barrier and does not affect the metabolism of levodopa within the central nervous system. Administering Rytary increases levels of dopamine in the brain which helps to relieve the symptoms of Parkinson's disease.
• Rytary belongs to the class of medicines known as dopaminergic antiparkinsonian agents. It may also be called a dopamine antiparkinsonian agent or a dopamine agonist.

2. Upsides

• May be used to treat Parkinson's disease.
• May also be used to treat post-encephalitic parkinsonism and symptomatic parkinsonism that may follow carbon monoxide intoxication or manganese intoxication.
• Rytary is an extended-release combination of carbidopa and levodopa which lasts longer in the body than immediate-release forms of carbidopa and levodopa such as Sinemet.
• Rytary is usually taken three times a day (up to a maximum of five times a day) compared with Sinemet which may be dosed up to eight times a day.
• The presence of carbidopa in Rytary means that more levodopa reaches the brain and less is converted into dopamine in the periphery which may also reduce the incidence of nausea and vomiting.
• May be taken with or without food.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Nausea, dizziness, headache, dry mouth, and insomnia are the most common side effects reported with Rytary.
• Dyskinesias (abnormal involuntary movements, including erratic writhing movements of the face, arms, legs, or trunk, rapid jerking, or slow and extended muscle spasms) and nausea can occur with Rytary. A dosage reduction may be required to reduce the severity of dyskinesias.
• Other adverse effects include chest pain, cardiac irregularities, low blood pressure, lack of energy, vein inflammation, gastrointestinal effects (eg, vomiting, diarrhea, constipation, dyspepsia), pain, cramps, rash, increased sweating, weight gain, or weight loss.
• Rytary has also been associated with psychotic-like behavior and hallucinations that may be accompanied by confusion and sleep disorders. Rytary may also affect thinking and behavior and cause agitation, delirium, delusions, and paranoia. Usually, people with a preexisting psychotic disorder should not be treated with Rytary.
• Rytary may affect impulse control and people may experience intense urges to gamble, spend money, eat, or have sex. These urges may decrease on dosage reduction or stopping the medication.
• The risk of melanoma is two to six times higher in people taking Rytary than in the general population. Periodic skin evaluations should be performed by appropriately qualified individuals.
• Not recommended for children or adolescents under the age of 18 years.
• For patients converting from immediate-release carbidopa/levodopa to Rytary, consult the product information for Rytary to find the recommended starting dose of Rytary based on the previous dosage of carbidopa/levodopa. For example, people previously taking 750mg to 949mg of levodopa in carbidopa/levodopa should start with 3 capsules of Rytary 36.25/145 three times a day.
• Should not be given within two weeks of nonselective monoamine oxidase (MAO) inhibitors such as isocarboxazid, phenelzine, and tranylcypromine. Rytary may be administered with the manufacturer's recommended dose of a selective MAO type B inhibitor such as selegiline.
• Contraindicated in people with a known hypersensitivity to any component of Rytary, and in patients with narrow-angle glaucoma, unless the intraocular pressure is well controlled and the person is monitored carefully. Regular blood tests and monitoring of liver, renal, and cardiovascular function are recommended in people taking Rytary for long periods.
• There is an increased risk of depression in people taking Rytary. Monitor people taking Rytary for the development of depression with concomitant suicidal tendencies.
• Administer cautiously to people with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic, or endocrine disease. This includes people with a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias. Cardiac function may need to be monitored in a facility with provisions for intensive cardiac care during the initial dosage titration.
• May increase the risk of upper gastrointestinal hemorrhages in patients with a history of peptic ulcers.
• There are reports of people suddenly falling asleep without prior warning of sleepiness while engaged in daily activities, including driving resulting in road traffic accidents. May occur soon after treatment initiation but has been reported as long as one year after the initiation of treatment.
• The dosage of Rytary needs to be individualized. The usual recommended starting dose in people who have not taken levodopa before is one 23.75/95 extended-release capsule taken orally three times a day for the first three days. On the fourth day, the dosage should be increased to one 36.25/145 capsule taken three times a day.
• Dose reductions or discontinuation of Rytary has been uncommonly associated with a symptom complex resembling neuroleptic malignant syndrome (NMS), which may be fatal. Symptoms include fever, hyperthermia, muscle rigidity, involuntary movements, altered consciousness, confusion, fast heartbeat, sweating, low or high blood pressure, and altered laboratory values, such as creatine phosphokinase. The dosage of Rytary should be tapered down slowly. Observe patients when the dosage of Rytary is reduced abruptly or discontinued, especially if the patient is also receiving antipsychotics.
• Rytary may cause laboratory test abnormalities such as elevations in liver function tests such as alkaline phosphatase, SGOT (AST), SGPT (ALT), lactic dehydrogenase (LDH), and bilirubin. Abnormalities in blood urea nitrogen (BUN) and positive Coombs test have also been reported. May cause false-positive reactions for urinary ketone bodies, false-negative tests using glucose-oxidase methods of testing for glucosuria, and rarely falsely diagnosed pheochromocytoma.
• The use of Rytary during pregnancy has not been adequately studied but there is evidence it crosses the human placental barrier, enters the fetus, and is metabolized. Animal studies have revealed both visceral and skeletal malformations. Weigh up the risks versus benefits before using during pregnancy. Use caution when using Rytary during breastfeeding as levodopa has been detected in human milk.
• Not currently available as a generic.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Rytary is an extended-release (long-lasting) medication that may be used for the treatment of Parkinson's disease that is available in four different strengths: Rytary 23.75/95, Rytary 36.25/145, Rytary 48.75/195, and Rytary 61.25/245. Nausea, dizziness, a headache, dry mouth, and insomnia are the most common side effects reported with Rytary and it has an advantage over immediate-release forms of carbidopa/levodopa (such as Sinemet) in that it only needs to be dosed three times a day.

5. Tips

• Rytary capsules should be swallowed whole and may be taken with or without food. Do not chew or crush Ryatary capsules. If you have difficulty swallowing Rytary capsules, carefully open the capsule then sprinkle the entire contents on a small amount of applesauce and swallow immediately. Do not store this applesauce/Rytary mixture for future use.
• Rytary is only available as a 1:4 ratio of carbidopa to levodopa. However, it is available as four different strengths: Rytary 23.75/95, Rytary 36.25/145, Rytary 48.75/195, and Rytary 61.25/245. Always check the label to ensure you are taking the right strength of Rytary. It may take a while for your doctor to find the right dosage for you.
• Rytary is a long-acting formulation that needs to be taken regularly. Take Rytary exactly as prescribed by your doctor; do not increase or decrease the dosage without their advice.
• The absorption of Rytary may be affected by a change to a high protein diet, excessive acidity, or by some supplements, such as iron salts (which may be contained in multivitamin tablets). Try to keep your diet consistent and talk to your doctor or pharmacist before taking any other medications or supplements.
• Be cautious when driving or operating machinery because Rytary may cause people to suddenly fall asleep without any prior warning, or prior feeling of drowsiness. Avoid alcohol or other medications, such as sedating antihistamines, that may also cause sedation.
• Rytary may cause your saliva, urine, or sweat to become discolored to red, brown, or black. Although this does not seem to have a clinically meaningful effect, garments may become discolored.
• Rytary may affect your impulse control and you may experience intense urges to gamble, spend money, eat, or have sex. Tell your doctor if this happens to you because a dosage reduction may decrease these urges.
• Rytary may increase your risk of developing skin cancers, such as melanoma. Protect your skin when going outside by wearing a hat and protective clothing, and apply sunblock to exposed areas of your skin. Ensure you get your skin checked for skin cancer at least once a year by an appropriately qualified individual.
• If you require surgery, Rytary may be continued as long as fluids and medication by mouth are permitted. If you have to temporarily discontinue treatment of Rytary, then you should be monitored for the appearance of NMS; symptoms include fever, hyperthermia, muscle rigidity, involuntary movements, altered consciousness, confusion, fast heartbeat, or sweating. Restart Rytary as soon as you are able.
• If you are of childbearing age you should use adequate contraception to ensure you do not become pregnant while taking Rytary If you inadvertently become pregnant, tell your doctor straight away so that you can be monitored throughout your pregnancy.

6. Response and effectiveness

• The absorption of levodopa may be delayed by up to two hours in some patients on a high protein/high calorie (fat) diet because levodopa competes with certain amino acids for transport across the gut wall.
• The presence of carbidopa in Rytary allows patients treated for Parkinson's disease to use much lower doses of levodopa (about 75% lower). Some people who have responded poorly to levodopa have improved on Rytary; most likely due to a decreased breakdown of levodopa caused by the administration of carbidopa rather than by a primary effect of carbidopa on the nervous system. Carbidopa does not enhance the intrinsic efficacy of levodopa.
• The decarboxylase-inhibiting activity of carbidopa is limited to extracerebral tissues, which makes more levodopa available for transport to the brain.
• The half-life of levodopa is about 50 minutes without carbidopa. With carbidopa, the half-life of levodopa is increased to about 1.5 hours.
• Rytary is available in a 1:4 ratio of carbidopa to levodopa but as four strengths Rytary 23.75/95, Rytary 36.25/145, Rytary 48.75/195, and Rytary 61.25/245mg. Studies have shown that peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 to 100 mg a day. People who receive less than this amount are more at risk of side effects such as nausea and vomiting.
• Following oral administration of Rytary, the maximum concentration of carbidopa in the blood occurs in approximately 3 hours, and levodopa, in one hour. Plasma concentrations of levodopa are maintained for about four to five hours before declining.
• After 30 weeks of treatment with Rytary, a change in baseline UPDRS (Unified Parkinson's Disease Rating Scale) score of 11.7 was reported for the 36.25/145 capsules taken three times daily, 12.9 for the 61.25/245 capsules taken three times daily, and 21.4 for the 97.5/390 capsules taken three times daily.

7. Interactions

Medicines that interact with Rytary may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Rytary. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with Rytary include:

• 5-hydroxytryptophan
• amisulpride
• antidepressants, such as tricyclic antidepressants (eg, amitriptyline) or monoamine oxidase inhibitors (eg, isocarboxazid, phenelzine, and tranylcypromine)
• any medication that lowers blood pressure, such as beta-blockers (eg, atenolol or sotalol), ACE inhibitors (such as captopril or enalapril), or diuretics (such as bendrofluazide or furosemide
• any medication that may cause drowsiness, such as benzodiazepines (eg, diazepam, lorazepam), first-generation antihistamines (such as doxylamine or promethazine), or opioids (such as codeine, morphine)
• cholesterol-lowering agents such as atorvastatin or simvastatin
• dopamine D2 receptor antagonists such as butyrophenones, phenothiazines, or thioxanthenes and atypical antipsychotics (eg, olanzapine, quetiapine, risperidone, ziprasidone)
• dopamine-depleting agents, such as reserpine or tetrabenazine
• iron salts or multivitamins that contain iron (can form chelates with Rytary and reduce its absorption)
• metoclopramide (has dopamine antagonistic properties)
• selegiline
• sodium oxybate
• vincristine.

Avoid drinking alcohol or taking illegal or recreational drugs while taking Rytary.

Rytary may be given to people receiving supplemental pyridoxine (vitamin B⁶) because carbidopa inhibits the pyridoxine-increased decarboxylation of levodopa.

Note that this list is not all-inclusive and includes only common medications that may interact with Rytary. You should refer to the prescribing information for Rytary for a complete list of interactions.

References

• Rytary (levodopa and carbidopa capsule, extended-release). Updated 12/2022. Impax Laboratories, Inc. https://www.drugs.com/pro/rytary.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Rytary only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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